The subject of the invention is the production of polymer alginate material, especially the production of alginate beads or films, the use of such alginate materials and biological implants that are enclosed in or coated with such alginate materials.
It is known that, with allogene or xenogene transplantations, immune responses of the host organism can be countered by microencapsulation of the transplant for the purpose of immunoisolating it (see F. Lim et al. in xe2x80x9cSciencexe2x80x9d, vol. 210, 1980, pp 908-910, H. A. Clayton et al. in xe2x80x9cActa Diabetol.xe2x80x9d, vol. 30, 1993, pp 181-189). Spherical alginate beads have proven their advantages in encapsulating allogene or xenogene, endocrine tissue (for example see T. Zekorn et al. in xe2x80x9cActa Diabetol.xe2x80x9d, vol. 29, 1992, pp 41-52, P. De Vos et al. in xe2x80x9cBiomaterialsxe2x80x9d, vol. 18, 1997, pp 273-278, C. Hasse et al. in xe2x80x9cExp. Clin. Endocrinol. Diabetesxe2x80x9d, vol. 105, 1997, pp 53-56, and in xe2x80x9cJ. Microencapsulationxe2x80x9d, vol. 14, 1997, pp 617-626). The alginates are Ca2+ or Ba2+ linked and especially effective in immuno-isolation if they are purified, ie as free as possible of mitogeneous contamination (see U. Zimmermann et al. in xe2x80x9cElectrophoresisxe2x80x9d, vol. 13, 1992, pp 269-274, G. Klxc3x6ck et al. in xe2x80x9cBiomaterialsxe2x80x9d, vol. 18, 1997, pp 707-713).
The transplantation of alginate encapsulated tissue is not only tested in animal experiments but is already being introduced in human medicine. Thus C. Hasse et al. in xe2x80x9cThe Lancetxe2x80x9d, vol. 350, 1997, p 1296, for example, describe microencapsulation in the case of an allogene parathyroid transplantation in the muscle tissue of two patients with permanent symptomatic hypoactivity of the parathyroid. After treatment with alginate immuno-isolated parathyroid tissue, it was possible for the patients to leave hospital without showing hypocalcaemic symptoms and without requiring therapy to suppress immune responses. Nevertheless, as before in animal experiments, the transplants were only effective for a limited time, which can be traced to the disappearance of the alginate enclosure.
From U.S. Pat. No. 5,429,821 we know of the formation of alginate coated transplants where, to increase alginate stability, Ca2+ linked alginate gel is cross-linked with L-poly-lysine or other physiologically acceptable, non-toxic polycations. The advantage of this technique is improved alginate stability. But cross-linking with L-poly-lysine is nevertheless a disadvantage, because the embedded transplant can trigger fibrosis, resulting in problems as in the use of unpurified alginates. Consequently, further treatment of the alginate gels is necessary to achieve biocompatibility of the transplant.
The stability of the transplanted alginate beads is a general problem that is also described by G. Klxc3x6ck et al. in xe2x80x9cBiomaterialsxe2x80x9d, vol. 18, 1997, pp 707-713, for example, and by P. De Vos in xe2x80x9cDiabetologiaxe2x80x9d, vol. 40, 1997, pp 262-270. Continuing clinical use of alginate encapsulated transplants calls for the development of more stable alginate beads.
The object of the invention is to propose a method for producing alginate material, especially for enclosing or coating transplants, that results in enhanced stability and reliability of the alginate material in practical conditions. It is also the object of the invention to propose new uses for such alginate material and new transplants provided with improved alginate material of this kind.
These objects are resolved by a method with the features of patent claim 1. Advantageous embodiments of the invention result from the attached claims.